原创力文档activating transcription factor-3 (atf3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (hsp90) inhibition转录激活因素3(atf3)函数作为一个肿瘤抑制结肠癌和上调后热休克蛋白90(一半)抑制.pdfVIP
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activating transcription factor-3 (atf3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (hsp90) inhibition转录激活因素3(atf3)函数作为一个肿瘤抑制结肠癌和上调后热休克蛋白90(一半)抑制
Hackl et al. BMC Cancer 2010, 10:668
/1471-2407/10/668
RESEARCH ARTICLE Open Access
Activating transcription factor-3 (ATF3) functions
as a tumor suppressor in colon cancer and is
up-regulated upon heat-shock protein 90 (Hsp90)
inhibition
1 1 1 1 1 2
Christina Hackl , Sven A Lang , Christian Moser , Akira Mori , Stefan Fichtner-Feigl , Claus Hellerbrand ,
3 1 1 1,4*
Wolfgang Dietmeier , Hans J Schlitt , Edward K Geissler , Oliver Stoeltzing
Abstract
Background: Activating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response.
However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic
effects have been described. Here we followed-up on our previous observation that inhibition of Hsp90 may
increase ATF3 expression and sought to determine the role of ATF3 in colon cancer.
Methods: Regulation of ATF3 was determined in cancer cells using signaling inhibitors and a heat-shock protein-
90 (Hsp90) antagonist. Human HCT116 cancer cells were stably transfected with an ATF3-shRNA or a luciferase-
shRNA expression plasmid and alterations in cell motility were assessed in migration assays. The impact of ATF3
down-regulation on cancer growth and metastasis were investigated in a subcutaneous tumor model, a model of
hepatic tumor growth and in a model of peritoneal carcinomatosis. Human colon cancer tissues were analyzed for
ATF3 expression.
Results: The results show that therapeutic Hsp90 inhibition substantially up-regulates the expression of ATF3 in
various cancer cells, including colon, gastric and pancreatic cancer. This effect was evident both
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